title: Rapamycin prevents drug seeking via disrupting reconsolidation of reward memory in rats.
abstract: The maladaptive drug memory developed between the drug-rewarding effect and environmental cues contributes to difficulty in preventing drug relapse. Established reward memories can be disrupted by pharmacologic interventions following their reactivation. Rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) kinase, has been proved to be involved in various memory consolidation. However, it is less well characterized in drug memory reconsolidation. Using a conditioned place preference (CPP) procedure, we examined the effects of systemically administered rapamycin on reconsolidation of drug memory in rats. We found that systemically administered rapamycin (0.1 or 10 mg/kg, i.p.) after re-exposure to drug-paired environment, dose dependently decreased the expression of CPP 1 d later, and the effect lasted for up to 14 d and could not be reversed by a priming injection of morphine. The effect of rapamycin on morphine-associated memory was specific to drug-paired context, and rapamycin had no effect on subsequent CPP expression when rats were exposed to saline-paired context or homecage. These results indicated that systemic administration of rapamycin after memory reactivation can persistently inhibit the drug seeking behaviour via disruption of morphine memory reconsolidation in rats. Additionally, the effect of rapamycin on memory reconsolidation was reproduced in cocaine CPP and alcohol CPP. Furthermore, rapamycin did not induce conditioned place aversion and had no effect on locomotor activity and anxiety behaviour. These findings suggest that rapamycin could erase the acquired drug CPP in rats, and that mTOR activity plays an important role in drug reconsolidation and is required for drug relapse.
authors.affiliation: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Wuhan University, Ministry of Education, and Wuhan University School of Pharmaceutical Sciences, Wuhan, Hubei 430071, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Lin
authors.forename: Lingqi
authors.initials: L
authors.lastname: Liu
authors.forename: Quan
authors.initials: Q
authors.lastname: Wen
authors.forename: Chunming
authors.initials: C
authors.lastname: Zheng
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.forename: Shuxian
authors.initials: S
authors.lastname: Peng
authors.forename: Yalun
authors.initials: Y
authors.lastname: Tan
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D003042:Cocaine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects; D003463:Cues; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051381:Rats; D012201:Reward; D020123:Sirolimus / Q000494:pharmacology*
chemical_list: D047428:Protein Kinase Inhibitors; D000431:Ethanol; D009020:Morphine; D003042:Cocaine; D020123:Sirolimus